Diabetes mellitus is a metabolic disorder in which the ability to utilize glucose is partly or completely lost. Since the introduction of insulin in the 1920's, continuous efforts have been made to improve the treatment of diabetes mellitus. Since people suffering from diabetes are subject to chronic treatment over several decades, there is a major need for safe, convenient and life quality improving insulin formulations.
In the treatment of diabetes mellitus, many varieties of insulin formulations have been suggested and used, such as regular insulin, isophane insulin (designated NPH), insulin zinc suspensions (such as Semilente®, Lente®, and Ultralent®), and biphasic isophane insulin. Some of the commercial available insulin formulations are characterized by a fast onset of action and other formulations have a relatively slow onset but show a more or less prolonged action. Fast-acting insulin formulations are usually solutions of insulin, while retarded acting insulin formulations can be suspensions containing insulin in crystalline and/or amorphous form precipitated by addition of zinc salts alone or by addition of protamine or by a combination of both. Within the last decade a number of human insulin analogues have been developed. They are designed for particular profiles of action, i.e. fast acting or prolonged action.
Another peptide expected to become very important in the treatment of diabetes is glucagon-like peptide-1 (GLP-1). Human GLP-1 is a 37 amino acid residue peptide originating from preproglucagon which is synthesized i.a. in the L-cells in the distal ileum, in the pancreas and in the brain. GLP-1 is an important gut hormone with regulatory function in glucose metabolism and gastrointestinal secretion and metabolism. GLP-1 stimulates insulin secretion in a glucose-dependant manner, stimulates insulin biosynthesis, promotes beta cell rescue, decreases glucagon secretion, gastric emptying and food intake. As the type 2 diabetes population is rapidly increasing in the world there is a much larger need for simpler administration of more effective drugs. A combination formulation comprising an insulin peptide and a GLP-1 peptide with a fixed ratio of the two pharmaceuticals may be a very efficacious treatment as well as one requiring less injections when administered to the same patient.
A combined treatment of insulin requiring diabetes comprising administration of insulin and GLP-1 is disclosed in WO 95/31214. Pre-mixed formulation of GLP-1 compounds and basal insulin are disclosed in WO 03/020201. Shelf stable pharmaceutical compositions comprising GLP-1, a basal insulin and surfactants are disclosed in WO 2006/051103.